Zachary Klaassen: Hi, my name is Zach Klaassen, urologic oncologist at the Georgia Cancer Center in Augusta, Georgia. We are at AUA 2025 in Las Vegas on UroToday. Pleased to be joined by Dr. Dan Petrylak, medical oncologist, and Dr. Steve Finkelstein, radiation oncologist. Gentlemen, thanks so much for joining us on UroToday.

Daniel Petrylak: Thank you.

Steven Finkelstein: Thank you so much for having us.

Zachary Klaassen: So we have some-- I mean, the last month in prostate cancer has been incredible. We've had another huge FDA approval, mCRPC PLUVICTO, prechemotherapy. So maybe, Dan, I'll start with you. Just bring us up to date on the data that led to that FDA approval from PSMAfore.

Daniel Petrylak: So this was a randomized trial of PLUVICTO, up to six cycles, versus best standard of care, which was a secondary anti-androgen. These are patients who had failed androgen deprivation therapy. And there was a really significantly different improvement-- or there was a significant improvement in radiographic progression-free survival in favor of PLUVICTO.

Patients could also cross over to the PLUVICTO if they had received the anti-androgen is there or they're on the control arm. So it's showing a really, really significant difference. The survival is not different, but that's to be expected because of the fact that these patients, 85% of these patients actually got PLUVICTO in this study.

Zachary Klaassen: And so, Steve, we're all excited about this. But there are some criteria to be a candidate for PLUVICTO. So maybe just walk through some of those nuances and that objective criteria.

Steven Finkelstein: Yeah, I think the most important thing for the audience would be that you have to be PSMA positive. And on the clinical trials, patients obtained a PSMA PET scan. And that was usually a gallium scan in the way that the trials were written. But the new trials and then the commercial space allows for either a PSMA PET by gallium or other methods. So as long as they have imaging that you can see on PSMA PET, these patients can be a candidate now for PLUVICTO.

And this is not, as Dan alluded to, this is not a drug that just got approved in this trial. It was approved in a previous trial in later patients. And I think what's really exciting is the fact that it's now approved in a space prechemotherapy, on label.

Zachary Klaassen: Yep. Let's get into the patient, I guess, selection but more tolerability. How have you guys seen is this going to be, in the trial, tolerability prechemo? Obviously, chemo has its side effects. Maybe talk a little about that, Dan, from a medical oncology perspective.

Daniel Petrylak: So I think the side effects are clearly different. I think the quality of life is better on PLUVICTO. However, I think you have to select your patient properly. As we know, PSMA is not necessarily expressed in liver, so this may not be the right treatment to use in those particular patients. You have to really look at the patient and see what their disease progression is, the sites of progression, and also their positivity of the PSMA PET scan, as Steve just mentioned.

So with PLUVICTO, you can have some issues with blood counts. And sometimes that can be difficult to treat because it can be permanent in some patients. It's rare, but it does happen. So I think you have to take that into consideration, what's the extent of marrow involvement. Either way with chemotherapy, as well as with PLUVICTO, that can be an issue.

And also, of course, what the patient's overall condition is. There are some patients, also from a selection standpoint, who don't want chemotherapy. But the way I view this is that we don't have ways of selecting, on a molecular basis, which of these treatments we should be using, chemotherapy or PLUVICTO.

And we really need more studies to understand that because clearly, now we have more tools in our tool kit, patients are benefiting from this, and the important thing is patient choice. Patients now can choose what they want and have an informed discussion with the physician and go forth with shared decision-making.

Zachary Klaassen: Yeah, great point. Steve, maybe I'll ask you this, with treatment sequencing, obviously, is what we all want to figure out, whether it be guided by PSMA PET positivity, genomics, et cetera. When we look at this now moving up in the disease space to essentially second line and we look at patients in the mHSPC setting, maybe they had triplet therapy. There's a lot going on. How do you see this fitting in and what that patient population may look like?

Steven Finkelstein: That's a terrific question. And I think all of us in the oncology field want to think about the pieces of sequencing. I think when we date back to the papers that Dan and I wrote, even so far now ago it seems, RADAR II, where we talked about therapeutic overlay, that we want to make sure patients get all of these agents if they need it and make sure that we don't burn bridges.

I think as you alluded to, if we're giving PLUVICTO later in the journey, it becomes harder because the disease burden is so that when you're treating these patients, it's not just about what the drug might do for side effects but what the cancer actually does. So we're very excited about moving this more upstream and giving patients the option of a radiopharmaceutical. And I think that will create a tidal wave of interest in the radiopharmaceuticals in this space.

I also think that it's a unique world that we live in, in that there's, for the first time, different agents with different mechanisms. And I think that we're in a place where I don't think we're going to abandon chemotherapy, but I think we need to almost play four-dimensional chess about how we can get our patient the best outcome by combining these agents, making sure they get it as a journey, not a destination.

Zachary Klaassen: Yeah.

Daniel Petrylak: It sort of reminds me of the Apollo Program. When you went to the moon, you didn't aim for where the moon is now. You aim for it where the moon was going to be in four days. And you have to think about your treatment of prostate cancer the same way. How am I going to treat this patient over the next 12 to 18 months? Where are these treatments going to be put into their overall armamentarium? What are the molecular markers that these patients need to have assessed, particularly with the PARP inhibitors, also with some of the androgen receptor mutations now that we're identifying.

And then what about combination therapy? Because we're using this as monotherapy. There's some exciting data looking at PLUVICTO combined with enzalutamide. Also PLUVICTO combined with checkpoint therapy. Checkpoint therapy is really active in this disease. We just published a paper with docetaxel and a checkpoint. Didn't really see a survival benefit compared to docetaxel alone. So I think that we have a really, really good opportunity to make a major impact in survival and quality of life.

Zachary Klaassen: Yeah, well said. Before we wrap up, I mean, just to touch on the multidisciplinary aspect of advanced prostate cancer in general. We're at a urology meeting. We've got a urologist, a rad ONC, and a med ONC sitting in the same room. And there's not a bad joke coming. But I think maybe just each touch on how this has really evolved over the last 5 to 10 years?

Daniel Petrylak: Well, I've had a terrific relationship with the urologists, both at Columbia, as well as at Yale now. And I work with Dr. Isaac Kim very, very closely and his colleagues in designing trials. My office is actually in the Urology Department, so we're able to converse about patients and studies very, very freely. And it really does help tremendously.

We also now have another leg incorporated, our nuclear medicine doc. We have regular rounds with our nuclear medicine physicians to talk about scans, to talk about also potential trials. So it's a collaborative effort. It only can mean a positive thing for the patients.

Zachary Klaassen: Absolutely. Steve?

Steven Finkelstein: I think it's so important to have multidisciplinary care. So as the National Director for Radiation Oncology for U.S. Urology Partners, one of the largest urology groups in the world, I think it's so important that I can go three feet to talk to my urology colleague and talk about the patient. It truly allows, in the community setting, that interplay back and forth.

And we have that interplay also with our medical oncology colleagues. So in Syracuse at one of our flagships at AMP, where I practice, we're able to talk with the medical oncologist, with the urologists, I'm the radiation oncologist, and all of us together are working in the best interest of the patient. I think if you do that, you'll achieve the best outcomes in prostate cancer care.

It worries me when we're just all off on our own little islands. And so I encourage patients to seek out care where they can have truly multidisciplinary clinics, especially when thinking about PLUVICTO.

Zachary Klaassen: Yeah, that's so well said. Gentlemen, fantastic conversation. I was looking forward to it. It did not disappoint. Thank you for your time on UroToday.

Daniel Petrylak: Thank you again so much for having us.

Zachary Klaassen: Of course.